Overview Of Heart Disease PDF

# OVERVIEW OF HEART DISEASE Although a wide range of diseases can affect the cardiovascular system, the pathophysiologic pathways that result in a "broken" heart can be distilled down to six principal mechanisms: - **Failure of the pump.** In the most common situation, the cardiac muscle contracts...

# OVERVIEW OF HEART DISEASE Although a wide range of diseases can affect the cardiovascular system, the pathophysiologic pathways that result in a "broken" heart can be distilled down to six principal mechanisms: - **Failure of the pump.** In the most common situation, the cardiac muscle contracts weakly and the chambers cannot empty properly—so-called systolic dysfunction. In some cases, the muscle cannot relax sufficiently to permit ventricular filling, resulting in diastolic dysfunction. - **Obstruction to flow.** Lesions that prevent valve opening (e.g., calcific aortic valve stenosis) or cause increased ventricular chamber pressures (e.g., systemic hypertension or aortic stenosis) can overwork the myocardium, which has to pump against the increased obstruction (as in valvular stenosis) or resistance (as in hypertension). - **Regurgitant flow.** Valve pathology that allows backward flow of blood results in increased volume workload and may overwhelm the pumping capacity of the affected chambers. - **Shunted flow.** Defects (congenital or acquired) that divert blood inappropriately from one chamber to another, or from one vessel to another, lead to pressure and volume overloads. - **Disorders of cardiac conduction.** Uncoordinated cardiac impulses or blocked conduction pathways can cause arrhythmias that slow contractions or prevent effective pumping altogether. - **Rupture of the heart or major vessel.** Loss of circulatory continuity (e.g., a gunshot wound through the thoracic aorta) may lead to massive blood loss, shock, and death. # HEART FAILURE Heart failure, often referred to as congestive heart failure (CHF), is the common end point for many forms of cardiac disease and is typically a progressive condition with a poor prognosis. CHF occurs when the heart cannot generate sufficient output to meet the metabolic demands of the tissues or can only do so at higher-than-normal filling pressures. In a minority of cases, heart failure is a consequence of greatly increased tissue demands, as in hyperthyroidism, or decreased oxygen-carrying capacity, as in anemia (high-output failure). The onset of CHF is sometimes abrupt, as in the setting of a large myocardial infarct or acute valve dysfunction. In most cases, however, CHF develops gradually and insidiously owing to the cumulative effects of chronic work overload or progressive loss of myocardial function. Heart failure may result from any cause that impairs the ability of the ventricle to fill with or eject blood. The inability to eject blood (systolic failure) results from inadequate myocardial contractile function, usually as a consequence of ischemic heart disease or hypertension. Diastolic failure refers to an inability of the heart to adequately relax and fill. This form of heart failure is called heart failure with preserved ejection fraction. It is said to exist when symptoms of heart failure are associated with left ventricular ejection fraction ≥50%. Approximately one-half of CHF cases are attributable to diastolic dysfunction, with a greater frequency seen in older adults, patients with diabetes, and women. When the failing heart can no longer efficiently pump blood, there is an increase in end-diastolic ventricular volumes, increased end-diastolic pressures, and elevated venous pressures. Thus, inadequate cardiac output-called forward failure is almost always accompanied by increased congestion of the venous circulation-that is, backward failure. Although the root problem in CHF is typically deficient cardiac function, virtually every other organ is eventually affected by some combination of forward and backward failure. Several homeostatic mechanisms are employed by the cardiovascular system to compensate for reduced myocardial contractility or increased hemodynamic burden: - **The Frank-Starling mechanism.** Increased filling volumes dilate the heart, thereby increasing actin-myosin cross-bridge formation and enhancing contractility and stroke volume. As long as the dilated ventricle is able to maintain cardiac output by this means, the patient is said to be in compensated heart failure. However, ventricular dilation comes at the expense of increased wall tension and also increases the oxygen requirements of an already-compromised myocardium. With time, the failing muscle is no longer able to propel sufficient blood to meet the needs of the body, and the patient develops decompensated heart failure. - **Activation of neurohumoral systems:** - Release of the neurotransmitter norepinephrine by the autonomic nervous system increases heart rate and augments myocardial contractility and vascular resistance. - Activation of the renin-angiotensin-aldosterone system spurs water and salt retention (augmenting circulatory volume) and increases vascular tone. - Release of atrial natriuretic peptide acts to balance the renin-angiotensin-aldosterone system through diuresis and vascular smooth muscle relaxation. - **Myocardial structural changes, including increased muscle mass.** Cardiac myocytes adapt to increased workload by assembling new sarcomeres, a change that is accompanied by myocyte enlargement (hypertrophy) - In pressure overload states (e.g., hypertension or valvular stenosis), new sarcomeres tend to be added parallel to the long axis of the myocytes, adjacent to existing sarcomeres. The growing muscle fiber diameter thus results in concentric hypertrophy, and the ventricular wall thickness increases without an increase in the size of the chamber. - In volume overload states (e.g., valvular regurgitation or shunts), the new sarcomeres are added in series with existing sarcomeres so that the muscle fiber length increases. Consequently, the ventricle tends to dilate, and the resulting wall thickness can be increased, normal, or decreased; thus, heart weight-rather than wall thickness-is the best measure of hypertrophy in volume-overloaded hearts. Compensatory hypertrophy comes at a cost. The oxygen requirements of hypertrophic myocardium are greater due to increased myocardial cell mass. Because the myocardial capillary bed does not expand sufficiently to meet the increased myocardial oxygen demands, the myocardium becomes vulnerable to ischemic injury. Pathologic compensatory cardiac hypertrophy is correlated with increased mortality; indeed, cardiac hypertrophy is an independent risk factor for sudden cardiac death. By contrast, the volume-loaded hypertrophy induced by regular aerobic exercise (physiologic hypertrophy) is typically accompanied by an increase in capillary density and decreased resting heart rate and blood pressure. These physiologic adaptations reduce overall cardiovascular morbidity and mortality. On the other hand, anaerobic exercise (e.g., weightlifting) is associated with pressure hypertrophy and may not have the same beneficial effects. # Left-Sided Heart Failure Heart failure can affect predominantly the left or right side of the heart or may involve both sides. The most common causes of left-sided cardiac failure are ischemic heart disease (IHD), systemic hypertension, mitral or aortic valve disease, and primary diseases of the myocardium (e.g., amyloidosis). The morphologic and clinical effects of left-sided CHF stem from diminished systemic perfusion and elevated back-pressures within the pulmonary circulation. # MORPHOLOGY - **Heart.** The gross cardiac findings depend on the underlying disease process; for example, myocardial infarction or valvular deformities may be present. With the exception of failure due to mitral valve stenosis or restrictive cardiomyopathies (described later), the left ventricle is usually hypertrophied and can be dilated, sometimes massively. Left ventricular dilation can result in mitral insufficiency and left atrial enlargement, which is associated with an increased incidence of atrial fibrillation. The microscopic changes in heart failure are nonspecific, consisting primarily of myocyte hypertrophy with interstitial fibrosis of variable severity. Superimposed on this background may be other lesions that contribute to the development of heart failure (e.g., recent or old myocardial infarction). - **Lungs.** In acute left-sided heart failure, rising pressure in the pulmonary veins is ultimately transmitted back to the capillaries and arteries of the lungs, resulting in congestion and edema as well as pleural effusion due to increased hydrostatic pressure in the venules of the visceral pleura. The lungs are heavy and wet and microscopically show perivascular and interstitial transudates, alveolar septal edema, and accumulation of edema fluid in the alveolar spaces. In chronic heart failure, variable numbers of red cells extravasate from the leaky capillaries into alveolar spaces, where they are phagocytosed by macrophages. The subsequent breakdown of red cells and hemoglobin leads to the appearance of hemosiderin-laden alveolar macrophages —so-called heart failure cells—that reflect previous episodes of pulmonary edema. # Clinical Features Dyspnea (shortness of breath) on exertion is usually the earliest and most significant symptom of left-sided heart failure; cough is also common as a consequence of fluid transudation into air spaces. As failure progresses, patients experience dyspnea when recumbent (orthopnea) because the supine position increases venous return from the lower extremities and also elevates the diaphragm. Orthopnea is typically relieved by sitting or standing, so patients usually sleep in a semiseated position. Paroxysmal nocturnal dyspnea is a particularly dramatic form of breathlessness, awakening patients from sleep with extreme dyspnea bordering on feelings of suffocation. Other manifestations of left ventricular failure include an enlarged heart (cardiomegaly), tachycardia, a third heart sound (S3), which represents rapid passive ventricular filling, and fine rales at the lung bases, caused by the opening of edematous pulmonary alveoli by inspired air. With progressive ventricular dilation, the papillary muscles are displaced outward, resulting in mitral regurgitation and a systolic murmur. Subsequent chronic dilation of the left atrium can cause atrial fibrillation due to firing from stretch sensitive ion channels. It is manifested by an "irregularly irregular" heartbeat. Such uncoordinated, chaotic atrial contractions reduce the atrial contribution to ventricular filling, thus reducing the ventricular stroke volume. Atrial fibrillation also causes stasis of the blood (particularly in the atrial appendage), frequently leading to the formation of thrombi that can shed emboli, causing infarction in other organs (e.g., stroke). Diminished cardiac output leads to decreased renal perfusion that in turn triggers the renin-angiotensin-aldosterone axis, increasing intravascular volume and pressures. However, with a failing heart, these compensatory effects exacerbate the pulmonary edema. With further progression of CHF, prerenal failure may supervene, with impaired excretion of wastes and increasing metabolic derangement. In severe CHF, diminished cerebral perfusion may manifest as hypoxic encephalopathy marked by irritability, diminished cognition, and restlessness that can progress to stupor and coma. Treatment for CHF is typically focused—at least initially—on correcting the underlying cause, for example, a valvular defect or inadequate cardiac perfusion. In lieu of such options, the clinical approach includes salt restriction or pharmacologic agents that variously reduce volume overload (e.g., diuretics), increase myocardial contractility (so-called "positive inotropes"), or reduce afterload (adrenergic blockade or inhibitors of angiotensin-converting enzymes). Angiotensin-converting enzyme inhibitors appear to benefit patients not only by opposing aldosterone-mediated salt and water retention but also by limiting cardiomyocyte hypertrophy and remodeling. # Right-Sided Heart Failure Right-sided heart failure is usually the consequence of left-sided heart failure, since any pressure increase in the pulmonary circulation inevitably produces an increased burden on the right side of the heart. Consequently, the causes of right-sided heart failure include all those that induce left-sided heart failure. Isolated right-sided heart failure is infrequent and typically occurs in patients with one of a variety of disorders affecting the lungs; hence, it is often referred to as cor pulmonale. In addition to parenchymal lung diseases, cor pulmonale may also arise secondary to disorders that affect the pulmonary vasculature, for example, primary pulmonary hypertension, recurrent pulmonary thromboembolism, or conditions that cause pulmonary vasoconstriction (obstructive sleep apnea). The common feature of these disorders is pulmonary hypertension (discussed later), which results in hypertrophy and dilation of the right side of the heart. In cor pulmonale, myocardial hypertrophy and dilation are generally confined to the right ventricle and atrium, although bulging of the ventricular septum to the left can reduce cardiac output by causing outflow tract obstruction. The major morphologic and clinical effects of pure right-sided heart failure differ from those of left-sided heart failure in that engorgement of the systemic and portal venous systems is typically the earliest and most significant symptom. # MORPHOLOGY - **Liver and Portal System.** The liver is usually increased in size and weight (congestive hepatomegaly). A cut section displays prominent passive congestion characterized by congested centrilobular areas surrounded by peripheral paler, noncongested parenchyma, a pattern referred to as nutmeg liver When left-sided heart failure is also present, severe central hypoxia produces centrilobular necrosis in addition to the sinusoidal congestion. With long-standing severe right-sided heart failure, the central areas can become fibrotic, creating so-called cardiac cirrhosis. Right-sided heart failure can also lead to elevated pressure in the portal vein and its tributaries (portal hypertension), with vascular congestion producing a tense, enlarged spleen (congestive splenomegaly). When severe, chronic passive congestion and attendant edema of the bowel wall may interfere with absorption of nutrients and medications. - **Pleural, Pericardial, and Peritoneal Spaces.** Systemic venous congestion due to right-sided heart failure can lead to transudates (effusions) in the pleural and pericardial spaces but usually does not cause pulmonary parenchymal edema. Pleural effusions are most pronounced when there is combined right-sided and left-sided heart failure, leading to elevated pulmonary and systemic venous pressures. A combination of hepatic congestion (with or without diminished albumin synthesis) and portal hypertension can lead to peritoneal transudates (ascites). When uncomplicated, effusions associated with right-sided CHF are transudates with a low protein content and lack of inflammatory cells. - **Subcutaneous Tissues.** Pitting edema of dependent portions of the body, especially the feet and lower legs, is a hallmark of right-sided CHF. In chronically bedridden patients, the edema may be primarily presacral. # Clinical Features Unlike left-sided heart failure, pure right-sided heart failure is not typically associated with respiratory symptoms. Instead, the clinical manifestations are related to systemic and portal venous congestion and include hepatic and splenic enlargement, peripheral edema, pleural effusion, and ascites. Venous congestion and hypoxia of the kidneys and brain due to right-sided heart failure can produce deficits comparable to those caused by the hypoperfusion of left-sided heart failure. Of note, cardiac decompensation is often marked by the appearance of biventricular CHF, encompassing features of both right-sided and left-sided heart failure. As CHF progresses, patients may become cyanotic and acidotic, as a consequence of decreased tissue perfusion resulting from both diminished cardiac output and increasing